1. Field of the Invention
This invention is concerned with a novel animal with a deficiency of neutrophil chemotactic factor LECT2. The animal of the invention is mouse for experiment and research, which has no LECT2 protein by lacking LECT2 gene in its partial or whole gene. This invention is also concerned with the novel animal for investigation in etiology analysis and the development in therapeutic procedures for diseases of liver, bone, brain, respiratory organs, circulation organs and immune response concerning LECT2 such as hepatitis, cirrosis, hepatic cancer, regeneration of liver tissue, bone metabolism, rheumatoid arthritis, brain diseases, vasculitis, atherosclerosis, reperfusion dysfunction by eschemia, renal failure.
2. Prior Art
Liver shows an important role in the storage of substances, detoxification, host defense against infection, and homeostatis for life. When liver functions decrease in activity according to hepatic injury such as hepatitis, cirrosis, hepatic cancer, cell proliferation hepatocytes is started for recovery to get normal function of the hepatocytes. Usually, hepatocytes do not show cell proliferation under the conditions of suppression of cell division. The cell proliferation starts on the regeneration of liver tissue by the damage of liver tissue Some cytokines such as TNF-alpha and IL-6 are related in the proliferation of hepatocytes. However, it is difficult to explain the regulation of cell proliferation of hepatocytes by only these cytokines (References 1-3). On the other hand, LECT2 expressed in hepatocytes in liver tissue may regulate liver functions (Reference 4).
LECT2 has been purified as a novel neutrophil chemotactic factor (Reference 5). It is the protein that acts in the differentiation of macrophages and is mainly expressed in liver tissue (Reference 4). mRNA and protein of LECT2 are mainly expressed in hepatocytes. This can be seen from histological observations of hepatocytes and cell lines of hepatocytes. Therefore, LECT2 seems to be related with liver functions. Indeed, the inventors show a decrease in LECT2 expression from a normal liver to a liver with cancer (References 6, 7).
ChondromodulinII has the same amino acid sequence to that of LECT2, which is the same gene and protein, showing the activation of proliferation of osteoblasts (Reference 8), suggesting that LECT2 is related with bone metabolism. Bone metabolism is essential for maintaining bone skeletons and is supported by balance between proliferation of osteoblast cells and osteocrast cells. It has not been clarified in detail, though some cytokines are related.
Thus, it has not been clarified in the etiology of diseases related with the dysfunction of the liver such as hepatitis, hepatic cancer, cirrosis, regeneration of liver tissue, autoimmune diseases, or abnormality of bone metabolism, but LECT2 may be an important agent in many important functions related with these diseases in vivo. Therefore, it is an important subject to analyze the role of LECT2 in vivo. Thus, preparation of model animal lacking LECT2 gene is strongly requested as an experimental model for investigating the effect of the subject protein lacking the LECT2 gene in its partial or whole gene.
As mentioned above, the inventors prepare the mouse lacking the LECT2 gene for analyzing the role of LECT2 in vivo. Then it will be possible to observe the physiological role of LECT2 directly. Thus, this invention of an animal model having a certain genetic background will show a clear etiology of diseases related with LECT2 and other diseases.
Procedures for dissolving the subject:
These inventors have investigated a recombination of specific vectors for LECT2 using a gene targeting method, which has been developed (9), and then this invention has been completed. Thus, this invention is concerned with mouse lacking the complete LECT2 gene by replacing the gene with a gene lacking LECT2 or another gene.
This invention is described as follows. The mouse prepared in this invention lacking the complete LECT2 gene by replacement of the gene with a gene lacking LECT2 or other genes, indicating the mouse has no LECT2 protein by lacking LECT2 gene in its partial or whole gene. The mouse in this invention is also concerned with the mouse having lack of the complete LECT2 gene in homozygotes or heterozygotes.